US2025049937A1PendingUtilityA1
Novel auristatin analogs and immunoconjugates thereof
Est. expiryDec 23, 2041(~15.4 yrs left)· nominal 20-yr term from priority
C07K 5/101A61P 35/00A61K 47/68031A61K 47/6855C07K 5/06052
54
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Claims
Abstract
The invention provides novel auristatin analogs and immunoconjugates thereof, as well as pharmaceutical compositions and methods of preparation and use for treating various diseases and disorders (e.g., cancer).
Claims
exact text as granted — not AI-modified1 . A compound having the structural formula (I):
or a pharmaceutically acceptable salt thereof,
wherein
R 1 is
wherein R 2 is a unsubstituted or substituted C 1 -C 6 alkyl, heteroalkyl, cycloalkyl or cycloheteroalkyl;
each of R a , R b and R c is selected from H and NR x R y , provided that only one of R a , R b and R c is NR x R y and each of the others is H;
each of R x and R y is independently selected from R, R r and L-R z , provided that when one of R x and R y is L-R z or R r , the other is R;
R 5 is H or CR′ 3 , wherein each R′ is independently H or F;
L is a linker;
R r is (C═O)—O—(CH 2 ) p —R v or (C═O)—(CH 2 ) q —R v ;
R v is R, OR, NHR, NR 2 , an aryl group or an amino acid;
p is 0, 1, 2, 3, 4, 5 or 6;
q is 0, 1, 2, 3, 4, 5 or 6;
R z comprises a functional or reactive group; and
R is H or a C 1 -C 3 alkyl.
2 . The compound of claim 1 , wherein
has the following chirality:
3 . The compound of claim 1 , wherein
has the following chirality:
4 . The compound of claim 1 , wherein R 5 is CH 3 .
5 . (canceled)
6 . The compound of claim 1 , wherein R 5 is H.
7 - 11 . (canceled)
12 . The compound of claim 1 , having the structural formula (III a ):
13 . The compound of claim 1 , having the structural formula (III b ):
14 . The compound of claim 12 , wherein R x is H and R y is H, having the structural formula (III 1 a ):
15 . The compound of claim 13 , wherein R x is H and R y is H, having the structural formula (III 1 a ) and (III 1 b ):
16 . The compound of claim 13 , wherein R x is H or CH 3 and R y is (C═O)—O—(CH 2 ) p —R v , wherein R′ is R, OR, NHR, NR 2 , an aryl group or an amino acid, and p is 0, 1, 2 or 3.
17 . The compound of claim 13 , wherein R x is H or CH 3 and R y is (C═O)—(CH 2 ) q —R v , wherein R v is R, OR, NHR, NR 2 , an aryl group or an amino acid and q is 0, 1, 2 or 3.
18 . The compound of claim 12 , wherein R y is L-R z , having the structural formula (III 2 a ):
19 . The compound of claim 13 , wherein R y is L-R z , having the structural formula (III 2 b ):
20 . The compound of claim 18 , wherein R x is H, having the structural formula (III 3 a ):
21 . The compound of claim 19 , wherein R x is H, having the structural formula (III 3 b ):
22 - 41 . (canceled)
42 . The compound of claim 1 , wherein R 1 is
wherein each of R 3 and R 4 is independently H or an unsubstituted or substituted C 1 -C 5 alkyl, or together with the N and C atoms they are boned to form a 5- to 7-membered heterocycloalkyl comprising one or more of O, N and S, optionally substituted with one or more of halogen atoms or C 1 -C 3 alkyl.
43 . The compound of claim 1 , wherein R 1 is
wherein each of R 3 and R 4 is independently H or an unsubstituted or substituted C 1 -C 5 alkyl, or together with the N and C atoms they are boned to form a 5- to 7-membered heterocycloalkyl comprising one or more of O, N and S, optionally substituted with one or more of halogen atoms or C 1 -C 3 alkyl.
44 - 47 . (canceled)
48 . The compound of claim 1 , wherein R 1 is selected from:
49 . The compound of claim 1 , wherein L is a noncleavable linker.
50 . The compound of claim 1 , wherein L is a cleavable linker.
51 - 56 . (canceled)
57 . A compound selected from the table below:
1
2
3
4
5
6
7
8
9
10
11
12, 13
14, 15
16, 17
18, 19
20
21
22
23
24
25
26
27
28
29
30
58 . A drug-linker conjugate formed by conjugation of a compound of claim 1 with a linker.
59 . An immunoconjugate formed by conjugation of a compound of claim 1 , via a linker, with an antigen binding moiety.
60 . An immunoconjugate having the structural formula (VI):
or a pharmaceutically acceptable salt thereof,
wherein
Ab represents an antigen binding moiety;
R 1 is
wherein R 2 is a unsubstituted or substituted C 1 -C 6 alkyl, heteroalkyl, cycloalkyl or cycloheteroalkyl;
each of R x and R y is independently selected from R and L-R z , provided that when one of R x and R y is NR z , the other is R;
R 5 is H or CR′ 3 , wherein each R′ is independently H or F;
L is a linker; and
R is H or a C 1 -C 3 alkyl;
i is an integer in the range of 1 to about 20.
61 - 82 . (canceled)
83 . A method for treating or reducing a disease or condition, comprising administering to a subject in need thereof a therapeutically effective amount of an immunoconjugate of claim 60 .
84 - 89 . (canceled)Join the waitlist — get patent alerts
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